Causes of Fetal Death

The etiology of fetal demise is unknown in 25-60% of all cases. In cases where a cause is clearly
identified, the cause of fetal death can be attributable to fetal, maternal, or placental pathology. One
prospective study attributed 64.9% of fetal death to placental pathology overall. The same study noted
higher rates of fetal demise secondary to placental pathology at late gestational age. [6]
A meta-analysis of 96 population-based studies found that maternal overweight and obesity was the
highest-ranking modifiable risk factor for stillbirth.[7, 8, 9] Advanced maternal age (>35 y) and maternal
smoking were also significant. Small size for gestational age and abruption were the highest-ranking
pregnancy disorder risk factors for stillbirth. Obstetric conditions and placental abnormalities were the
most common causes of stillbirth in one population-based study, with a higher number of stillbirths
associated with obstetric complications occurring in non-Hispanic black women. [10] Preexisting diabetes
and hypertension are also important contributors to stillbirth. [11]

Maternal

Prolonged pregnancy (>42 wk)

Diabetes (poorly controlled)
Systemic lupus erythematosus
Antiphospholipid syndrome
Infection
Hypertension
Preeclampsia
Eclampsia
Hemoglobinopathy
Advanced maternal age
Rh disease
Uterine rupture
Maternal trauma or death
Inherited thrombophilias

Fetal

Multiple gestations
Intrauterine growth restriction
Congenital abnormality
Genetic abnormality
Infection (ie, parvovirus B19, CMV, Listeria)
Hydrops

Placental

Cord accident
Abruption
Premature rupture of membranes
Vasa previa
Fetomaternal hemorrhage
Placental insufficiency

Risk factors (weak predictive value)

African American race

Advanced maternal age
History of fetal demise
Maternal infertility
History of small for gestational age infant

Small for gestational age infant

Obesity
Paternal age

Management of Fetal Death

Once the diagnosis of fetal demise has been confirmed, the patient should be informed of her condition.
Often, allowing the mother to see the lack of cardiac activity helps her to accept the diagnosis.
Termination of pregnancy should be offered after diagnosis. Patient responses vary in regard to this
recommendation; some wish to begin induction immediately, while others wish to delay induction for a
period of hours or days until they are emotionally prepared.
When a dead fetus has been in utero for 3-4 weeks, fibrinogen levels may drop, leading to a
coagulopathy.[3] This is rarely a problem because of earlier recognition and induction. In some cases of
twin pregnancies, induction after the death of a twin may be delayed to allow the viable twin to mature.
Induction may be accomplished with preinduction cervical ripening followed by intravenous oxytocin
(see Cervical Ripening). Patients with a history of a prior cesarean delivery should be treated cautiously
because of the risk of uterine rupture, just as in any birth following cesarean delivery (see Vaginal Birth
After Cesarean Delivery). The risk of uterine rupture during induction for fetal demise in the late second
and early third trimester is unknown.[4]
Early fetal demise may be managed with laminaria insertion followed by dilatation and evacuation. In
women with fetal death before 28 weeks' gestation, induction may be accomplished using prostaglandin
E2 vaginal suppositories (10-20 mg q4-6h), misoprostol (ie, prostaglandin E1) vaginally or orally (400 mcg
q4-6h), and/or oxytocin (preferred in women with prior uterine surgery).
Mifepristone 200 mg orally followed by misoprostol 400 mcg every 4-6 hours orally or vaginally appears to
be the most efficacious and results in the shortest time to delivery.[5] In settings in which mifepristone is
unavailable, misoprostol alone is also highly effective. For women with a prior cesarean delivery after 28
weeks gestation, mechanical ripening can be performed with a Foley catheter, and induction can be
continued with oxytocin.
Pain management in patients undergoing induction of labor for fetal demise is an important part of patient
care. Often, a morphine or hydromorphone patient-controlled analgesia device is sufficient for successful
pain control. Should a patient desire superior pain control to intravenous narcotics, epidural anesthesia
should be offered.

Maternal Studies

Maternal studies that should also be considered during the workup of a fetal demise include the following:

Diabetes testing using hemoglobin A1C and a fasting blood glucose

Syphilis screening using the VDRL or rapid plasma reagent test
Thyroid function testing (ie, TSH, FT4)
Urine toxicology screening
The above tests have traditionally been a part of an evaluation for the etiology of fetal demise. If diabetes
screening has been performed during the prenatal period, repeat testing for diabetes is probably not
necessary. Similarly, if the patient has no signs or symptoms of thyroid disease, thyroid dysfunction is
unlikely to be the cause of the demise. However, these tests are inexpensive and normal results may be
reassuring to the patient.
Additional tests that should be considered are as follows:

Antibody screening
CBC count with platelet count
Kleihauer-Betke test
Laboratory tests for antiphospholipid syndrome: See Antiphospholipid Antibody Syndrome and
Pregnancy.

Inherited thrombophilia panel

o
The enthusiasm for laboratory testing for inherited thrombophilias for adverse pregnancy
outcome is waning. Inherited thrombophilias are common in the general population but are probably
rare causes of fetal demise. A multicenter, prospective, observational cohort study concluded that
there was no association between prothrombin G20210A mutation and pregnancy loss, preeclampsia,
abruption, or SGA neonates in a low-risk population. [15] The current ACOG Practice Bulletin,
Management of Stillbirth, is now recommending inherited thrombophilia testing only in selected cases.
[16]
In a more recent ACOG Practice Bulletin, Inherited Thrombophilias in Pregnancy, there is no
recommendation to screen for inherited thrombophilias with pregnancy loss. [17]
o
While some authorities recommend maternal testing in all cases of fetal demise, a more
selective approach is to limit testing to patients who have a history of venous thrombosis, positive
family history, severe placental pathology, severe preeclampsia in the second or early third trimester,
abruption, or significant intrauterine growth retardation. The value of thrombophilia testing in any
circumstance in obstetrics has recently been questioned. [18, 19]

Infection: See Bacterial Infections and Pregnancy. Infection is a cause of fetal demise. The
frequency is higher in developing countries. Autopsy and histologic evaluation of the placenta is
probably the best way to document an infectious etiology for a fetal demise.
Authority opinions vary as to which panel of tests is appropriate. Traditionally, most authorities have
recommended obtaining TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus)
antibody titers. In reality, this is rarely helpful in the diagnosis. In addition, it is questionable whether
cytomegalovirus virus causes fetal demise. If no obvious cause for the demise is established or if clinical
signs or symptoms suggest infection, consider testing for (1) cytomegalovirus (acute and chronic titers),
(2) rubella virus (acute and chronic titers, if not immune), (3) parvovirus (acute and chronic titers), and
(4) Toxoplasmosis gondii (acute and chronic titers) and (5) syphilis. A more cost-effective approach is to
limit testing for cytomegalovirus, rubella virus, and T gondii to those patients in whom clinical findings
suggest the possibility of intrauterine infection (ie, those with intrauterine growth restriction, microcephaly